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GLP-1 RAs significantly reduce cardiovascular death and stroke, while SGLT2 inhibitors markedly lower heart failure and cardiovascular hospitalizations in type 2 diabetes.
Choosing an antidiabetic may be as important for the heart as it is for glycemic control, according to a large systematic review and network meta-analysis showing that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter 2 (SGLT2) inhibitors offer distinct but complementary cardiovascular (CV) benefits in adults with type 2 diabetes mellitus (T2DM).
The review synthesized evidence from 133 randomized controlled trials involving 289,558 participants (mean age 64.7 years), making it one of the most comprehensive comparisons of CV outcomes across antidiabetic drug classes. Researchers screened 10,514 records from PubMed (Medline), Embase, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL). The analysis included studies evaluating GLP-1 RAs, SGLT2 inhibitors, dipeptidyl peptidase 4 (DPP-4) inhibitors, insulin, metformin, sulfonylureas, and thiazolidinediones.
Using a random-effects network meta-analysis with Stata version 18 and assessing study quality with the Cochrane RoB 2.0 tool, investigators compared the effects of these therapies on CV mortality, myocardial infarction, stroke, heart failure, hospitalization for CV events, and unstable angina. Among all drug classes, GLP-1 RAs stood out for reducing CV mortality by 15% (risk ratio [RR] 0.85) and stroke by 17% (RR 0.83), with high-certainty evidence supporting both benefits. Meanwhile, SGLT2 inhibitors illustrated the strongest protection against heart failure, lowering its risk by 36% (RR 0.64), and reduced hospitalization for CV events by 28% (RR 0.72).
Both outcomes were supported by high-certainty evidence, underscoring the class's established role in preventing heart failure-related complications. An indirect network comparison also suggested lower CV mortality with DPP-4 inhibitors than with GLP-1 RAs. However, the authors cautioned that this observation was based on an imbalanced treatment network and must not be interpreted as definitive comparative evidence. Rather than identifying a single "best" therapy, the findings highlight that different antidiabetic drug classes excel in different CV outcomes.
GLP-1 RAs appear particularly valuable for reducing CV death and stroke, whereas SGLT2 inhibitors yield superior protection against heart failure and CV hospitalization. The investigators conclude that treatment selection should extend beyond glucose lowering and incorporate individual CV risk, comorbidities, and cost-effectiveness, enabling a more personalized approach to improving both CV and metabolic outcomes in T2DM.
Diabetology & Metabolic Syndrome
Comparative cardiovascular efficacy of antidiabetic therapies in type 2 diabetes: a systematic review and network meta-analysis of randomized trials
Donya Mohammadi et al.
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